The clinical utility of antiarrhythmic drugs does not correlate closely to the known effects of these drugs on the electrophysiologic properties of isolated cardiac fibers. This lack of correlation may be partially due to an incomplete understanding of the electrophysiologic effects of the drugs. The proposed study seeks to enhance our understanding of the mode of action of antiarrhythmic drugs by separating drugs effects into those resulting in alterations in steady-state properties and those resulting in alterations in the kinetic properties of the various components of action potential. The second major objective is to test the significance of these alterations in the intact heart. Maximum rate of depolarization, action potential duration, and effective refractory period will be studied in isolated ventricular and Purkinje fibers by microelectrode techniques. Conduction velocity and refractoriness will be studied in in vivo dog hearts by recordings of atrial, His bundle, and ventricular electrograms. The effects of partial depolarization and shortened diastolic intervals on drug-induced changes in electrophysiologic parameters will be assessed by increasing the potassium concentration in the extracellular fluid, by inducing progressively earlier premature responses, and by changing the heart rate. By identifying and separating these various drug effects, we should be able to classify the drugs more precisely than is permitted by our existing knowledge. It is hoped that the results obtained in this study will enable us to cater our choice of antiarrhythmic drugs to individual, specific clinical situations and thereby improve not only our basic understanding of the electrophysiologic changes induced by the antiarrhythmic drugs, but also their clinical utility.